VAL-010 Revalidation Procedure

1. Revalidation Categories

1.1. Process Revalidation

With the exception of sterile/aseptic processes, process revalidation is NOT frequent as validated status is maintained via a change control process.  The need for any revalidation outside of the change control process will be considered in response to repeated or unexplained batch failures or any adverse analytical trends.

1.2. Cleaning Revalidation

There is NO need to revalidate the process unless it is clear that the effectiveness of the cleaning procedures is inadequate or where significant changes in the manufacturing equipment or process have occurred.

1.3. Analytical Methods Revalidation

The routine revalidation of analytical methods is NOT necessary.  Revalidation will therefore normally result from the recurrence of analytical problems or excessive out of specification results associated with the analytical method.

1.4. Revalidation of Pharmacopeial methods is NOT necessary, but need to verify when such methods are updated

1.5. Equipment and Systems Re-qualification

If the Equipment/system has NOT been to subject to any major change or repeated unexplained failures the Equipment/system is considered to remain qualified and NO need for revalidation.

2. Initiation

2.1. It is the responsibility of the Validation Committee to provide an overall plan describing and defining the subject for revalidation based on the initial Validation of the equipment/process/system.  The criticality of the equipment/process/system, plus a knowledge of its inherent tendency to change, are considered when establishing the equipment/process/system revalidation programme.  The revalidation requirements are documented as part of the Validation report at the time of initial validation but may be modified over time when further knowledge of the equipment/process/system is gained.

2.2. Revalidation is required by the cGMP to be carried out on annual basis on all critical processes or when significant changes have been made to the equipment/process/system. Revalidation activities are usually preceded by a major preventative maintenance/calibration programme conducted by the Maintenance Department.

3. Changes that warrant Revalidation include

3.1. In simplest sense, a change is one that may impact safety, purity, identity, effectiveness or quality of the product, for example:

a. Changes to Master processing instruction

b. Changes to raw material suppliers or components

c. Changes to formulation or batch proportion

d. Introduction of new equipment or utilities

e. After extensive preventative maintenance work

f. Replacement of spare parts (different make)

4. Basic Steps during Revalidation

4.1. Validation committee to determination of Revalidation qualification tests required and time frame -done as part of Performance Qualification during initial validation.

4.2. Validation team to Prepare and maintain Revalidation Master Plan

4.3. Preparation and distribution of annual revalidation schedule

4.4. Issue of revalidation protocols

4.5. Coordination of preventative maintenance / recalibration / revalidation activities

4.6. Consult the Change Request log for equipment/system of any changes conducted since the last validation/revalidation and include in the revalidation report.

4.7. Validation Manager to Analyse the Change Request Log and determine if any additional revalidation tests required

4.8. Update and/or Issue of Equipment Checklists and revalidation test protocols

4.9. Conducting of revalidation qualification tests according to protocol, e.g. Chemical analysis of samples would be the responsibility of the Laboratory Manager.

4.10. Validation committee to approve the revalidated equipment/systems for use by production after completion of revalidation studies when all acceptance criteria have been met.  (Relevant Production Manager/Process Manager should be always notified.)

4.11. Review and approval of completed revalidation qualification tests file.

5. Revalidation Activities and Specific Responsibilities

5.1. It is the responsibility of the validation manager to provide the annual revalidation schedule.  This defines dates, activities and time frames when these activities are to be carried out in consultation with production schedules.  When preparing the schedule, refer to the most recent past schedule and ensure timings are within one month from previous revalidation.

5.2. Prior to the conducting of the revalidation tests as documented in the protocols, the Validation staff has to asses the changes that have been conducted over the previous year and determine, in consultation with the Validation Manager, if any additional revalidation studies are required.

5.3. The Validation staff is also responsible in coordinating with other departments to ensure that work is carried out according to schedules and actual studies follow the set protocols

5.4. The Validation staff is also responsible in coordinating with other departments to ensure that work is carried out according to schedules and actual studies follow the set protocols.

5.5. Following the preventative maintenance and calibration programme, a checklist for the equipment is to be filled out and a test run of the equipment/process/system is to be run by the team member of the Maintenance department prior to the hand over to the Validation Department to conduct the actual revalidation qualification tests.

6. Revalidation Protocols

Revalidation Protocols are used to highlight the Test Objective, Acceptance Criteria, Test Method, and the results obtained.

7. Revalidation Timing

Revalidation schedule should be prepared taking into account the current production activities, which will determine the availability of the equipment/process/system. Therefore, studies are to be conducted in the time frame of plus or minus one month of the most recent past revalidation, (i.e. 11-13months). If an extension beyond that date occurs without revalidation being conducted, the  equipment/process/system cannot be used for production activities without the specific documented approval of the Quality Assurance Manager.

8.  Equipment Checklist

An Equipment Checklist is used to ensure that all parameters are set correctly after any maintenance/adjustments have been made. The principle is to ensure that the equipment/process/system has not altered from the original, validated parameters.  Checklists are developed during the Operation & Performance Qualification by the Project Team for new equipment/processes/systems.

The checklist is stored with the Validation Department to ensure that current versions are maintained and issued by the validation staff to the Maintenance team prior to the revalidation activities.  The Equipment Checklists are approved by the Maintenance Department.

9. Revalidation Discrepancy Forms

Where a problem occurs, such as acceptance criteria not being met, a Validation Discrepancy Form (Form-370) must be filled out detailing the discrepancy the action that has been taken to address the discrepancy and a sign off to indicate that the actions have been satisfactorily completed and are effective in addressing the problem. For production batches used under revalidation activities a Deviation Report (SOP QMS-035) is raised if the acceptance criteria was not met and a copy of DR is attached to the Discrepancy form.

10. Release of Revalidated Equipment

If all physical testing is successful at the completion of the revalidation program, conditional release may be granted to the Production Manager via Validation staff carried out the revalidation. At the same time, a DR is to be raised to ensure that no product is released to the market until the Revalidation protocol is signed off.

11. Preparation of the Revalidation File

The Revalidation file provides the documented evidence that the equipment, process or systems are performing to their predetermined use as stated in each test function.  In addition, a summary of all    the changes and performance checks carried out since the last revalidation campaign is included.

 The file is compiled by Validation staff and checked by validation manager  within 8 working days of the maintenance, calibration, checklist and test functions being completed then it is circulated to members of the Validation Committee for review and approval.

Revalidation file comprises of the following sections:

11.1. Summary of Activities

A summary list of all the registered forms from the Change to Control System and an outline of the Revalidation Programme are prepared by the validation staff.

11.2. Revalidation Report – Final Review & Approval document:

It is a document that summarises the overall test objectives, test functions performed and an overall conclusion for a successful revalidation program.  It is the    document in the Revalidation file that the Validation Committee reviews, approves and signs off.

11.3. Test Functions:  This section is the main body of the file.  It contains a series of test functions, which have been selected by the Validation Committee to be challenged during Revalidation.  Each test protocol is made up with the following areas:

a. Process Description

b. Test Objectives

c. Acceptance Criteria

d. Method

e. Results

f. Conclusion

g. Attachments

All raw data obtained from external calibrated measuring devices. Data is reviewed and recorded in the result section of the protocol.  The results must agree with what is stated in the acceptance criteria before proceeding to the next test function.

(Note: The number of test functions will vary depending on the process.)

If a study is required to be repeated for any reason, it must be recorded on a Validation Discrepancy Form, and data from the failed study is to be filed in the Additional Information section.

12. Flow Chart – Revalidation Activities

13. Summary of Changes